Castanospermine
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MedKoo CAT#: 329644

CAS#: 79831-76-8 (free base)

Description: Castanospermine is an indolizidine alkaloid first isolated from the seeds of Castanospermum australe. It is a potent inhibitor of some glucosidase enzymes and has antiviral activity in vitro and in mouse models. Castanospermine was a lead to celgosivir.


Chemical Structure

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Castanospermine
CAS# 79831-76-8 (free base)

Theoretical Analysis

MedKoo Cat#: 329644
Name: Castanospermine
CAS#: 79831-76-8 (free base)
Chemical Formula: C8H15NO4
Exact Mass: 189.1001
Molecular Weight: 189.211
Elemental Analysis: C, 50.78; H, 7.99; N, 7.40; O, 33.82

Price and Availability

Size Price Availability Quantity
10.0mg USD 250.0 2 Weeks
25.0mg USD 450.0 2 Weeks
100.0mg USD 850.0 2 Weeks
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Related CAS #: 141117-12-6 (HCl)   79831-76-8 (free base)    

Synonym: Castanospermine

IUPAC/Chemical Name: (1S,6S,7R,8R,8aR)-1,2,3,5,6,7,8,8a-octahydroindolizine-1,6,7,8-tetrol

InChi Key: JDVVGAQPNNXQDW-TVNFTVLESA-N

InChi Code: InChI=1S/C8H15NO4/c10-4-1-2-9-3-5(11)7(12)8(13)6(4)9/h4-8,10-13H,1-3H2/t4-,5-,6+,7+,8+/m0/s1

SMILES Code: O[C@H]1CCN2C[C@H](O)[C@@H](O)[C@H](O)[C@@]12[H]

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Product Data:

Biological target: Castanospermine inhibits all forms of α- and β-glucosidases, especially glucosidase.
In vitro activity: Previous studies suggested that castanospermine, a pharmacological inhibitor of ER α-glucosidases, blocks trimming of N-linked carbohydrates and abrogates DEN-1 infection by preventing proper processing of the envelope glycoproteins. As a first step towards evaluating the utility of castanospermine as a broad-spectrum antiviral against DEN, it was assessed its ability to inhibit the DEN-2 strain 16681, which replicates efficiently in a range of cell lines including BHK-21 and Huh-7 cells. Treatment of cells with castanospermine inhibited the yield of infectious virus in a dose-dependent manner (Fig. 1A, B, and C). A higher concentration of castanospermine was required to inhibit the production of infectious DEN-2 in the Huh-7 human hepatoma cell line (50% inhibitory concentration [IC50], 85.7 μM) than in BHK-21 cells (IC50, 1 μM). The IC50 of castanospermine in BHK-21 cells was relatively independent of the inoculating dose of DEN, as similar values were observed over a broad range of multiplicities of infection (Fig. 1B). As observed previously in Neuro 2a cells, castanospermine treatment efficiently slowed the electrophoretic mobility of DEN prM, one of the glycosylated structural proteins. This difference in size between medium- and castanospermine-treated cells was restored after incubation of both proteins with endo H glycosidase (Fig. 1D). Reference: J Virol. 2005 Jul;79(14):8698-706. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/15994763/
In vivo activity: To further evaluate the protective activity of castanospermine, its ability to prevent mortality was assessed in highly lethal DEN and WNV challenge models in mice. A/J mice infected intracranially with 105 PFU of a mouse-adapted DEN-2 strain uniformly developed hind limb paralysis and succumbed to fatal central nervous system infection within 11 days of inoculation (Fig. 5A). A/J mice that were treated with castanospermine for 10 days showed marked reduction in morbidity and mortality. A/J mice treated with 0.2 mg (10 mg/kg of body weight), 1 mg (50 mg/kg), and 5 mg (250 mg/kg) per day had survival rates of 25, 90, and 85%, respectively, whereas mice treated with vehicle had a 0% survival rate (Fig. 5A, P < 0.0001 for all three doses). Of note, higher doses of castanospermine (25 mg or 1.25 g/kg) caused adverse effects including diarrhea and weight loss (data not shown). Given its efficacy in preventing lethal DEN infection in mice, we also tested its inhibitory activity, in vivo, against WNV. Based on the in vitro studies, we predicted that castanospermine would not significantly inhibit WNV-induced mortality. Moreover, because WNV infection is more severe in immunocompromised mice, if castanospermine had even a mildly immunosuppressive effect, we would expect increased mortality rates. Interestingly, treatment of mice with several doses of castanospermine had no effect, adverse or beneficial, on mortality after WNV infection (Fig. 5B and data not shown). Reference: J Virol. 2005 Jul;79(14):8698-706. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/15994763/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 528.51
Water 100.0 528.51

Preparing Stock Solutions

The following data is based on the product molecular weight 189.211 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
In vitro protocol: 1. Whitby K, Pierson TC, Geiss B, Lane K, Engle M, Zhou Y, Doms RW, Diamond MS. Castanospermine, a potent inhibitor of dengue virus infection in vitro and in vivo. J Virol. 2005 Jul;79(14):8698-706. doi: 10.1128/JVI.79.14.8698-8706.2005. PMID: 15994763; PMCID: PMC1168722. 2. Clarke EC, Nofchissey RA, Ye C, Bradfute SB. The iminosugars celgosivir, castanospermine and UV-4 inhibit SARS-CoV-2 replication. Glycobiology. 2021 May 3;31(4):378-384. doi: 10.1093/glycob/cwaa091. PMID: 32985653; PMCID: PMC7543591.
In vivo protocol: 1. Whitby K, Pierson TC, Geiss B, Lane K, Engle M, Zhou Y, Doms RW, Diamond MS. Castanospermine, a potent inhibitor of dengue virus infection in vitro and in vivo. J Virol. 2005 Jul;79(14):8698-706. doi: 10.1128/JVI.79.14.8698-8706.2005. PMID: 15994763; PMCID: PMC1168722. 2. Tharappel AM, Cheng Y, Holmes EH, Ostrander GK, Tang H. Castanospermine reduces Zika virus infection-associated seizure by inhibiting both the viral load and inflammation in mouse models. Antiviral Res. 2020 Nov;183:104935. doi: 10.1016/j.antiviral.2020.104935. Epub 2020 Sep 16. PMID: 32949636; PMCID: PMC7492813.

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1: Hibberd AD, Clark DA, Trevillian PR, Mcelduff P. Interaction between castanospermine an immunosuppressant and cyclosporin A in rat cardiac transplantation. World J Transplant. 2016 Mar 24;6(1):206-14. doi: 10.5500/wjt.v6.i1.206. PubMed PMID: 27011919; PubMed Central PMCID: PMC4801797.

2: Tiwari DK, Bharadwaj KC, Puranik VG, Tiwari DK. Divergent total synthesis of 1,6,8a-tri-epi-castanospermine and 1-deoxy-6,8a-di-epi-castanospermine from substituted azetidin-2-one (β-lactam), involving a cascade sequence of reactions as a key step. Org Biomol Chem. 2014 Oct 7;12(37):7389-96. doi: 10.1039/c4ob00948g. PubMed PMID: 25134486.

3: Hibberd AD, Trevillian PR, Clark DA, McElduff P, Cowden WB. The effects of Castanospermine, an oligosaccharide processing inhibitor, on mononuclear/endothelial cell binding and the expression of cell adhesion molecules. Transpl Immunol. 2012 Aug;27(1):39-47. doi: 10.1016/j.trim.2012.05.002. Epub 2012 May 27. PubMed PMID: 22647882.

4: Liu G, Wu TJ, Ruan YP, Huang PQ. A flexible approach to azasugars: asymmetric total syntheses of (+)-castanospermine, (+)-7-deoxy-6-epi-castanospermine, and (+)-1-epi-castanospermine. Chemistry. 2010 May 17;16(19):5755-68. doi: 10.1002/chem.200903490. PubMed PMID: 20379975.

5: Yun H, Kim J, Sim J, Lee S, Han YT, Chang DJ, Kim DD, Suh YG. Asymmetric syntheses of 1-deoxy-6,8a-di-epi-castanospermine and 1-deoxy-6-epi-castanospermine. J Org Chem. 2012 Jun 15;77(12):5389-93. doi: 10.1021/jo300309z. Epub 2012 May 25. PubMed PMID: 22612538.

6: Malik M, Witkowski G, Jarosz S. Carboxybenzyl group as an o-nucleophile in the C-H allylic oxidation: total synthesis of (-)-castanospermine. Org Lett. 2014 Jul 18;16(14):3816-9. doi: 10.1021/ol501730p. Epub 2014 Jul 8. PubMed PMID: 25004105.

7: Sánchez-Fernández EM, Álvarez E, Ortiz Mellet C, García Fernández JM. Synthesis of multibranched australine derivatives from reducing castanospermine analogues through the Amadori rearrangement of gem-diamine intermediates: selective inhibitors of β-glucosidase. J Org Chem. 2014 Dec 5;79(23):11722-8. doi: 10.1021/jo5025283. Epub 2014 Nov 20. PubMed PMID: 25390345.

8: Wojtowicz K, Januchowski R, Sosińska P, Nowicki M, Zabel M. Effect of brefeldin A and castanospermine on resistant cell lines as supplements in anticancer therapy. Oncol Rep. 2016 May;35(5):2896-906. doi: 10.3892/or.2016.4656. Epub 2016 Mar 7. PubMed PMID: 26985570.

9: Allan G, Ouadid-Ahidouch H, Sanchez-Fernandez EM, Risquez-Cuadro R, Fernandez JM, Ortiz-Mellet C, Ahidouch A. New castanospermine glycoside analogues inhibit breast cancer cell proliferation and induce apoptosis without affecting normal cells. PLoS One. 2013 Oct 4;8(10):e76411. doi: 10.1371/journal.pone.0076411. eCollection 2013. PubMed PMID: 24124558; PubMed Central PMCID: PMC3790671.

10: Hong YP, Chen C, Guo WY, Zhao L, Mei FC, Xiang MW, Wang WX. Effects of Castanospermine on Inflammatory Response in a Rat Model of Experimental Severe Acute Pancreatitis. Arch Med Res. 2016 Aug;47(6):436-445. doi: 10.1016/j.arcmed.2016.11.007. PubMed PMID: 27986123.

11: Saul R, Molyneux RJ, Elbein AD. Studies on the mechanism of castanospermine inhibition of alpha- and beta-glucosidases. Arch Biochem Biophys. 1984 May 1;230(2):668-75. PubMed PMID: 6424575.

12: Ruprecht RM, Mullaney S, Andersen J, Bronson R. In vivo analysis of castanospermine, a candidate antiretroviral agent. J Acquir Immune Defic Syndr. 1989;2(2):149-57. PubMed PMID: 2495348.

13: Ruprecht RM, Bernard LD, Bronson R, Gama Sosa MA, Mullaney S. Castanospermine vs. its 6-O-butanoyl analog: a comparison of toxicity and antiviral activity in vitro and in vivo. J Acquir Immune Defic Syndr. 1991;4(1):48-55. PubMed PMID: 1984055.

14: Whitby K, Pierson TC, Geiss B, Lane K, Engle M, Zhou Y, Doms RW, Diamond MS. Castanospermine, a potent inhibitor of dengue virus infection in vitro and in vivo. J Virol. 2005 Jul;79(14):8698-706. PubMed PMID: 15994763; PubMed Central PMCID: PMC1168722.

15: Campbell BC, Molyneux RJ, Jones KC. Differential inhibition by castanospermine of various insect disaccharidases. J Chem Ecol. 1987 Jul;13(7):1759-70. doi: 10.1007/BF00980216. PubMed PMID: 24302343.

16: Saul R, Chambers JP, Molyneux RJ, Elbein AD. Castanospermine, a tetrahydroxylated alkaloid that inhibits beta-glucosidase and beta-glucocerebrosidase. Arch Biochem Biophys. 1983 Mar;221(2):593-7. PubMed PMID: 6404222.

17: Yee CS, Schwab ED, Lehr JE, Quigley M, Pienta KJ. The effect of castanospermine on the metastatic properties of prostate cancer cells. Anticancer Res. 1997 Sep-Oct;17(5A):3659-63. PubMed PMID: 9413219.

18: Nichols EJ, Manger R, Hakomori SI, Rohrschneider LR. Transformation by the oncogene v-fms: the effects of castanospermine on transformation-related parameters. Exp Cell Res. 1987 Dec;173(2):486-95. PubMed PMID: 2826191.

19: Stegelmeier BL, Molyneux RJ, Elbein AD, James LF. The lesions of locoweed (Astragalus mollissimus), swainsonine, and castanospermine in rats. Vet Pathol. 1995 May;32(3):289-98. PubMed PMID: 7604496.

20: Kato A, Hirokami Y, Kinami K, Tsuji Y, Miyawaki S, Adachi I, Hollinshead J, Nash RJ, Kiappes JL, Zitzmann N, Cha JK, Molyneux RJ, Fleet GW, Asano N. Isolation and SAR studies of bicyclic iminosugars from Castanospermum australe as glycosidase inhibitors. Phytochemistry. 2015 Mar;111:124-31. doi: 10.1016/j.phytochem.2014.12.011. Epub 2015 Jan 9. PubMed PMID: 25583438.